JAC-Antimicrobial Resistance最新文献

Objectives: Non-typhoidal Salmonella (NTS) commonly causes a self-limiting illness but invasive disease (iNTS) can be life-threatening. Antimicrobial resistance (AMR) increases the risk of mortality. This systematic review aimed to estimate the proportion of NTS isolated in those attending healthcare services, serovar burden, AMR, serovar-specific AMR, and case fatality rate (CFR) in India, Bangladesh, Sri Lanka and Vietnam.

Methods: The review included quantitative studies on NTS and AMR from 1980 to 2020 but excluded studies unrelated to humans or selected countries. Data were extracted from articles identified from Ovid SP, Web of Science, Wiley Cochrane Library, Elsevier Scopus and WHO Global Index Medicus. The Joanna Briggs Institute Critical Appraisal Tools Checklist for Prevalence Studies was used for risk-of-bias assessment. Meta-analyses were performed for the proportion of NTS isolated, the proportion of specific serovars isolated, percentage of AMR and CFR.

Results: Six thousand and twenty-six isolates (79 serovars) were identified from 73 studies, with Salmonella enterica serovar Typhimurium being the most common. Of the 73 selected studies, 46% were hospital/laboratory surveillance studies, examining the aetiology of invasive or non-invasive infections. The pooled proportion estimate for non-iNTS was 2.1% (95% CI: 1.2%-3.2%) and for iNTS was 0.3% (95% CI: 0.1%-0.5%). The pooled CFR was 14.9% (95% CI: 4.0%-29.6%). Pooled resistance estimates for ampicillin, ceftriaxone, chloramphenicol, ciprofloxacin, co-trimoxazole, nalidixic acid and azithromycin were calculated. MDR iNTS was less prevalent in India [22.3% (95% CI: 0.0%-66.8%)] than in Vietnam [41.2% (95% CI: 33.6%-49.3%)]. Heterogeneity of studies was high as the majority were observational surveillance studies.

Conclusions: Despite data scarcity in some countries, this review highlights the continued contribution of NTS infection to disease burden, compounded by high AMR rates.

Objectives: With the global spread of antimicrobial resistance, treating urinary tract infections (UTIs) is becoming more challenging. Clinical data on UTI outcomes are scarce in cases with antimicrobial treatment mismatching the uropathogens' in vitro susceptibility profiles. We explored the association of (mis)matching antimicrobial treatment and clinical outcomes among patients with either ESBL-producing Enterobacterales (ESBL-PE) or non-ESBL-PE identified in urine samples.

Patients and methods: In 2015-2019, we recruited 18-65-year-old patients with laboratory-confirmed, community-acquired ESBL-PE (n = 130) or non-ESBL-PE (n = 187) UTI. Our study involved collecting data on in vitro susceptibility profiles, antimicrobial therapy (microbiological match/mismatch) and clinical outcomes, and a follow-up of relapses/reinfections.

Results: Non-beta-lactam co-resistance was found more frequent among ESBL-PE than non-ESBL-PE isolates. The initial antimicrobial matched the in vitro susceptibility for 91.6% (164/179) of those with non-ESBL-PE and 46.9% (38/81) with ESBL-PE UTI (P < 0.001). The clinical cure rates in the non-ESBL-PE and ESBL-PE UTI groups were 82.6% (142/172) and 62.2% (74/119) (P < 0.001) for all, 87.3% (131/150) and 83.3% (30/36) for those treated with matching antimicrobials, and 33.3% (5/15) and 41.9% (18/43) for those given mismatching antimicrobials, respectively. Mismatching antimicrobial therapy was not associated with relapse/reinfection over the 3-month follow-up (P = 0.943).

Conclusions: In our data, (mis)matching microbiological susceptibility is only partially associated with the clinical outcome of UTI: microbiological matching appears to predict clinical cure better than mismatching predicts clinical failure.

Background: Cefiderocol, a novel siderophore cephalosporin, is a promising therapeutic option for infections caused by multidrug-resistant Pseudomonas aeruginosa. We evaluated the activity of cefiderocol against carbapenem-resistant P. aeruginosa (Cr-Pa) isolates and investigated the potential mechanisms involved in resistance.

Methods: 108 CR-Pa isolates collected from patients without prior exposure to the substance were studied. MICs of cefiderocol were determined by broth microdilution using iron-depleted cation-adjusted Mueller-Hinton broth. Whole genome sequencing was performed to investigate the potential resistance mechanisms by comparing resistant and susceptible P. aeruginosa isolates and identifying unique mutations in the resistant group.

Results: Of the 108 isolates, nine were resistant to cefiderocol with MIC values ranging from 4 to 32 mg/L. The genetic analysis revealed a broad spectrum of mutations in the resistant isolates associated with iron uptake systems, efflux pumps, AmpC β-lactamase and penicillin-binding proteins. The most frequently observed mutations among the resistant isolates were located in fptA, fpvB and chtA. Notably, the presence of carbapenemases did not correlate with cefiderocol resistance.

Conclusions: Our findings show the low prevalence of cefiderocol resistance among CR-Pa isolates, showing its potential as an effective treatment option. However, the complex genetic landscape of resistance mechanisms, particularly mutations affecting iron transport and other TonB-dependent receptors, requires continuous monitoring and functional analyses to identify and manage potential resistance mechanisms. This study provides a foundation for future research to improve antimicrobial resistance prediction and develop targeted therapies against CR-Pa.

Background: Our study aimed to assess whether there was a relationship between graduating from higher-ranked medical schools and the rate of prescribing antibiotics among Medicare Part D providers in the USA.

Methods: The study obtained data from the Medicare Part D Prescribers (FY2013-2021) and the Doctor and Clinicians National repositories. A regression model was fitted to assess the relationship between provider medical school ranking and the rate of antibiotic days supplied per 100 beneficiaries at the provider level.

Results: A total of 197 540 providers were included. No association was found between the medical school ranking and the rate of antibiotics days supplied per 100 beneficiaries. Instead, the type of provider is associated with the prescription rates. Hospitalists and Emergency Medicine providers had fewer days supplied per 100 beneficiaries than Family Medicine providers. In contrast, students, more experienced providers (>20 years since medical school graduation) and females had more days supplied per 100 beneficiaries.

Conclusion: Our study highlights the need for robust outpatient stewardship interventions and incorporating an outcome-based approach to antibiotic stewardship curricula in medical and mid-level provider schools.

Background: Ivacaftor exhibits anti-staphylococcal properties but does not clear Staphylococcus aureus from the lungs of people with cystic fibrosis (pwCF). We assessed whether exposure to therapeutic concentrations of ivacaftor could allow S. aureus to form small colony variants (SCVs), a phenotype commonly associated with bacterial persistence.

Methods: Humanized G551D-CFTR (hG551D) rats were treated with ivacaftor for 7 days. Concentrations in the plasma, epithelial lining fluid and lung tissue lysate were measured using LC-MS/MS. Survival of S. aureus during ivacaftor treatment was assessed in an hG551D rat model of lung infection. S. aureus adaptation to therapeutic concentrations of ivacaftor was investigated in vitro by serial passage in the presence of 10 µM ivacaftor. Bacterial survival in the presence of antimicrobials was evaluated using growth curves and density assays.

Results: Ivacaftor plasma concentrations of treated hG551D rats reached 3.488 ± 1.118 µM, with more variable concentrations in the epithelial lining fluid and lung tissue lysate. During S. aureus infection, ivacaftor-treated hG551D rats returned similar numbers of bacteria from the lung, compared with vehicle-treated controls. Exposure of S. aureus to ivacaftor in vitro led to the formation of ivacaftor-tolerant SCVs with an unstable phenotype and increased antibiotic tolerance.

Conclusions: Treatment with ivacaftor did not alter S. aureus burden in the cystic fibrosis rat and led to the formation of tolerant SCVs in vitro, suggesting that development of an SCV phenotype may allow S. aureus to persist in the cystic fibrosis lung during ivacaftor therapy.

Background: Antibiotic resistance is a major public health threat, especially in nursing homes (NHs). Nursing home nurses (NHNs) can play a crucial role in antimicrobial stewardship (AMS), but research on their opinions regarding potential expanded AMS roles is limited.

Objectives: To identify different profiles of NHNs according to their opinions on the potential evolution of their AMS roles and to study facilitators/barriers to implementing new AMS roles and the demographic and professional characteristics associated with these profiles.

Methods: Data were collected from a national cross-sectional online survey conducted from May to July 2022 among French NHNs. Profiles were identified via hierarchical clustering. Factors associated with the identified profiles were studied via Fisher's exact tests.

Results: Among the 922 participants included in the analysis, three distinct profiles were identified. NHNs 'more favourable to the evolution of the AMS role' (40% of the sample) expressed strong support for the potential evolution of their AMS role. NHNs 'moderately favourable to the evolution of the AMS role' (46%) were less prone to reinforce discussion with general practitioners about antibiotic prescription. NHNs 'less favourable to the evolution of the AMS role' (14%) showed little or no agreement regarding several potential new AMS roles. Being a head nurse was associated with more favourable opinions on the evolution of the AMS role as opposed to practicing in NHs connected to a hospital.

Conclusions: These findings could help healthcare managers and policy-makers tailor the implementation of these new roles among NHNs, if they prove effective and safe.

Strategies and policies to tackle the global public health threat of antimicrobial resistance are increasingly addressing antimicrobial use prescribing practices in both the human and animal health sectors. Veterinarians' antibiotic prescribing practices are influenced by different factors and conditioned by the context within which antibiotic prescribing decisions are made, complexifying the implementation of behaviour change interventions. A better understanding of these factors could therefore help in the design and application of such interventions. Meta-ethnography was used to explore the antibiotic prescribing behaviour of veterinarians in different contexts and to construct a new conceptual framework. A search was conducted in PubMed, Web of Science Core Collection and SciELO Citation Index between 2016 and 2024. The final sample consisted of 29 articles, 27 of which were selected from the 561 articles identified in the search and 2 of which were added by the authors. The results were synthesized and presented through four contextual situations influencing antibiotic prescribing by livestock veterinarians: priorities and pressures, uncertain field conditions, systemic challenges and an enabling environment. The results are presented as a conceptual framework that views veterinarians' antibiotic prescribing behaviour as dynamic, adapting in response to the different contextual situations they encounter. The findings provide an integrated and contextualized understanding of veterinarians' antibiotic prescribing behaviours, which could be implemented to facilitate the development and application of future antimicrobial stewardship interventions.

Background: Antibiotics are the most prescribed drugs for children worldwide, but overuse and misuse have led to an increase in antibiotic resistance. Antimicrobial stewardship programmes (ASPs) have proven feasible in reducing inappropriate antimicrobial use. The study aimed at evaluating the impact and sustainability of an ASP with multiple interventions over 8 years.

Methods: This quasi-experimental study was conducted between 2014 and 2022 in the paediatric acute care unit of Padua University Hospital. Demographic and clinical data were retrieved from the electronic clinical records. Daily prescriptions were collected and analysed based on the AWaRe classification and using days of therapy (DOT) out of 1000 patient days (DOT/1000PDs). The primary outcome was to assess the change in overall antibiotic consumption and of access and watch antibiotics, stratifying patients with and without comorbidities. Trends in antibiotic consumption (DOTs/1000PD) were assessed using joinpoint regression analysis.

Findings: A total of 3118 children were included. Total antibiotic consumption remained stable and low in patients without comorbidities, ∼300 DOT/1000PDs, whereas a statistically significant constant reduction was observed in children with comorbidities, from almost 500 DOT/1000PPDs to <400 DOT/1000PDs. Access consumption increased in both groups of patients, whereas watch consumption constantly decreased, although statistically significant only in children with comorbidities.

Interpretation: Implementing a multistep ASP has proven feasible and sustainable in improving antibiotic prescriptions for previously healthy and fragile children. All the implemented interventions were low cost, and with efficient use of resources, ensuring an ASP that was effective, practical, and easily replicable and implementable in various healthcare settings.

Introduction: Escherichia coli ST1193 is an emerging high-risk clone associated with the production of plasmid-mediated CTX-type extended-spectrum β-lactamases. However, this clone has seldom been found to contain plasmids carrying carbapenemase genes. We report two epidemiologically unlinked multidrug-resistant (MDR) clinical isolates of E. coli ST1193 with plasmids harbouring NDM-type carbapenemase genes from the Gulf region.

Methods: The isolates were identified by MALDI-TOF MS and antibiotic susceptibility testing was performed using the VITEK 2/Phoenix system. A conjugation experiment was performed to assess the transferability of the resistance plasmids. Genomic DNA of both isolates was subject to Illumina sequencing; one isolate was also sequenced using Oxford Nanopore technology. Bioinformatics analyses were performed to detect antimicrobial resistance genes, and to annotate the genetic context of the NDM genes.

Results and conclusions: Both isolates were resistant to carbapenems using phenotypic tests. Conjugation experiment confirmed that NDM-5-encoding plasmids of both strains could be transferred to the recipient cells. The completed NDM-5-encoding plasmid of E. coli isolate FQ71 was highly similar to several plasmids from ST410 isolates in the NCBI database. Genomic analysis revealed the presence of transposase genes and transposons in the flanking regions of the NDM genes in the plasmids. Since carbapenems constitute first-line agents for the treatment of serious infections caused by ESBL producers, E. coli ST1193 isolates co-producing ESBL and NDM-type carbapenemases represent a serious challenge for antimicrobial stewardship and infection control programmes.

Introduction: Resistance to first-line antibiotics among urinary tract infections continues to rise, but how neighbourhood-level socioeconomic status impacts this risk remains unclear. We examined the effect of neighbourhood-level income on a patient's risk of having a uropathogen non-susceptible to trimethoprim/sulfamethoxazole (TMP/SMX) or nitrofurantoin.

Methods: We used electronic health record data and antibiotic susceptibility test results for urinary Escherichia coli and Klebsiella pneumoniae collected at Emory Healthcare outpatient facilities in greater Atlanta between October 2022 and September 2023. We determined patients' block group median household income (MHI) using their residential addresses and 2017-21 US census data. We performed a logistic regression with a priori risk factors using a generalized estimating equation, with subgroup analysis by organism and for patients with diabetes mellitus.

Results: We included 9325 urine E. coli and K. pneumoniae isolates from 3867 outpatients. Compared to uropathogenic E. coli, K. pneumoniae were more likely to be non-susceptible to nitrofurantoin (P < 0.001) and less likely to be non-susceptible to TMP/SMX (P < 0.001). Compared to the lowest MHI quintile, patients in the highest MHI quintile neighbourhoods had 0.78 odds of harbouring a non-susceptible uropathogen (95% CI: 0.64, 0.95) after controlling for patient age, sex and race/ethnicity, along with neighbourhood-level characteristics. This association was stronger for K. pneumoniae infections and non-significant among people with diabetes.

Conclusions: Higher neighbourhood-level MHI was associated with lower individual risk of harbouring a first-line antibiotic-non-susceptible uropathogen.